2. Origin and propagation in nerve impulse. BIOS 0501B (Group A) DBS, PU, Sem 5; 2015

Transcription

1 2. Origin and propagation in nerve impulse BIOS 0501B (Group A) DBS, PU, Sem 5; 2015

2 Diffusion: cell membrane Speed? Passive Lipid soluble Oxygen Carbon di oxide Water soluble (uses protein channels) Very fast if you are water or similar size (every second RBC takes and throws out 100 times the volume of cell) Slower as your size increases

3 Diffusion: protein channels Simplest form will work as an open gate. If you fit, you can go. No restriction, no regulation. Some are gated ; that is, they have a gate like structure/conformation

4 Na & K channels Sodium channel Only 0.3 by 0.5 nanometer in diameter Inner surfaces of this channel are strongly negatively charged Can pull sodium ions through them and dehydrates in the process Potassium channel Smaller: 0.3 by 0.3 nanometer Not negatively charged Allows passage of hydrated potassium These strong negative charges can pull small dehydrated sodium ions into these channels, actually pulling the sodium ions away from their hydrating water molecules. Guyton & Hall 11 th ed

5 Voltage gating Gating Molecular conformation of the gate or of its chemical bonds responds to the electrical potential across the cell membrane. Chemical (ligand) gating: Binding of a chemical substance (a ligand) causes a conformational or chemical bonding change in the protein molecule that opens or closes the gate Mechanical gating: Responds to mechanical stimuli

6 Gating characteristic: All or none

7 Diffusion is not directional Rate of diffusion So what would be the net diffusion? Net diffusion (C o C i ) C o = Concentration outside; C i = Concentration outside

8 Nernst potential Applying electricity gradient changes the equilibrium Until new equilibrium attained At 37 C the electrical difference that will balance a given concentration difference of univalent ions (like Na + ) can be calculated by Nernst equation EMF (in millivolt) = ± 61 log (C 1 /C 2 ) C 1 = Conc on one side; C 2 = Conc on other side

9 Active transport What happens when A cell need large concentration of a substance in the intracellular fluid even though the extracellular fluid contains only a small concentration potassium ions Conversely, it is important to keep the concentrations of other ions very low inside the cell even though their concentrations in the extracellular fluid are great. sodium ions You need active transport for moving ions uphill Primary when ATP is used directly Secondary - energy is derived secondarily from energy that has been stored in the form of ionic concentration differences of secondary molecular or ionic substances between the two sides of a cell membrane

10 Na + -K + pump The carrier protein is a complex of two separate globular proteins α subunit β subunit It has three receptor sites for binding sodium ions on the portion of the protein that protrudes to the inside of the cell It has two receptor sites for potassium ions on the outside The inside portion of this protein near the sodium binding sites has ATPase activity When two potassium ions bind on the outside of the carrier protein and three sodium ions bind on the inside, the ATPase function of the protein becomes activated. This then cleaves one molecule of ATP, splitting it to adenosine diphosphate (ADP) and liberating a high-energy phosphate bond of energy. This liberated energy is then believed to cause a chemical and conformational change in the protein carrier molecule, extruding the three sodium ions to the outside and the two potassium ions to the inside. Guyton & Hall, 11 th edition, Chapter 4, Page 53

11 Na + -K + pump

12 Na + -K + pump Mol Cell Biol, Lodish, 5 th ed

13 Controlling Cell Volume Cells are full of various kinds of organic molecules Most of them are negatively charged They attract positively charged ions inside the cell That promotes osmosis To balance this cells pump Na + out of the cells (3 Na + out for 2 K + in; a net loss of 1) That solves the osmosis problem But makes inside of the cells negatively charged That s membrane potential

14 Membrane potentials K + K + K + K + Diffusion potential Na + Na + Na + Na + Na + Na + Na + Na + 61mV Semi permeable membrane mV + + K + K + K + K + K + K + K + K + K + K + Na + Na + Na + Outside Inside

15 Measuring membrane potential Easy Get a big nerve Insert one electrode inside And keep one out next to the membrane Measure voltage using very fancy oscilloscope To establish the normal resting potential of 90 millivolts inside the nerve fiber only about 1/3,000,000 to 1/100,000,000 of the total positive charges inside the fiber needs to be transferred Equally small number is needed to reverse 90 millivolts to as much as +35 millivolts within as little as 1/10,000 of a second.

16 The resting potential K + ions slowly leak through K + pore channels The membrane has a poor permeability to Na + ions so they cannot get in to the neurone This brings about the membrane potential of neurones As the K + leaks out the inside of the resting cell becomes more negatively charged

17 A potential difference exists across every cell s plasma membrane Negative pole cytoplasmic side Positive pole extracellular fluid side When a neuron is not being stimulated, it maintains a resting potential Ranges from 40 to 90 millivolts (mv) Average about 70 mv There is a mathematical explanation using Nernst Potential

18 Calculations based on Nernst potential

19 The uniqueness of neurons Uniqueness of neurons compared with other cells is not the production and maintenance of the resting membrane potential Rather the sudden temporary disruptions to the resting membrane potential that occur in response to stimuli 2 types of changes Graded potentials Action potentials

20 Graded potential (GP) Small transient changes in membrane potential due to activation of gated ion channels Each gated channel is selective Most are closed in the normal resting cell Voltage-gated ion channels Excited by changes in membrane potential Chemically-gated or ligand-gated channels Changes in conformation by binding of ligands Mechanically gated channels Excited by mechanical changes Depolarization makes the membrane potential more positive Hyperpolarization makes it more negative These small changes result in graded potentials They die out within a short distance

21 Types of GP

22 GP is magnitude dependant

23 Depolarize

24 Spreading depolarization

25 Action potential Action potentials Result when depolarization reaches the threshold potential ( 55 mv) Depolarizations bring a neuron closer to the threshold Hyperpolarizations move the neuron further from the threshold Caused by voltage-gated ion channels Voltage-gated Na + channels Voltage-gated K + channels

26 Action potential

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28 Voltage-gated Na + channels Activation gate and inactivation gate At rest, activation gate closed, inactivation gate open Transient influx of Na + causes the membrane to depolarize Voltage-gated K + channels Single activation gate that is closed in the resting state K + channel opens slowly Efflux of K + repolarizes the membrane The action potential has three phases Rising, falling, and undershoot Action potentials are always separate, all-or-none events with the same amplitude Do not add up or interfere with each other

29 Sodium channel -70 mv -50 mv to +30mV +30 mv to -70mV

30 Potassium channel

31 Na + & K + channels 31

32 Propagation of action potentials Each action potential, in its rising phase, reflects a reversal in membrane polarity Positive charges due to influx of Na + can depolarize the adjacent region to threshold And so the next region produces its own action potential Meanwhile, the previous region repolarizes back to the resting membrane potential Signal does not go back toward cell body Two ways to increase velocity of conduction Axon has a large diameter Less resistance to current flow Found primarily in invertebrates Axon is myelinated Action potential is only produced at the nodes of Ranvier Impulse jumps from node to node

33 Unidirectionality

34 Refractory period The membrane potential falls below the resting potential of 70mV. It is said to be hyperpolarised Gradually active pumping of the ions (K + in and Na + out) restores the resting potential During this period no impulses can pass along that part of the membrane This is called the refractory period when the neuron resists another action potential. The absolute refractory period is the first part of the period in which the membrane can not produce an action potential. The relative refractory period is the second part in which it take a stronger than usual stimulus to trigger an action potential.

35 Nerve Impulse Transmission 35

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37 Few points The all-or-none law states that the amplitude and velocity of an action potential are independent of the intensity of the stimulus that initiated it. Action potentials are equal in intensity and speed within a given neuron. Saltatory conduction is the word used to describe this jumping of the action potential from node to node. Provides rapid conduction of impulses Conserves energy for the cell Tetrodotoxin is a common neurotoxin that works by blocking Na + channel

38 The way it was done Giant squid Get a very big nerve Can be 1mm in diameter

39 Clamp it In using this apparatus, two electrodes are inserted into the nerve fiber. One of these is to measure the voltage of the membrane potential, and the other is to conduct electrical current into or out of the nerve fiber.

40 Get Nobel Hodgkin and Huxley 1963

41 Multiple source for images Read Guyton & Hall Sherwood et al

42 Size: Na + vs K + The hydrated form of the potassium ion is considerably smaller than the hydrated form of sodium because the sodium ion attracts far more water molecules than does potassium. Therefore, the smaller hydrated potassium ions can pass easily through this small channel, whereas the larger hydrated sodium ions are rejected, thus providing selective permeability for a specific ion. Guyton & Hall, 11 th edition, Chapter 4, Page 48